In optical imaging of biological tissues, especially the living human eye, it has been shown in recent years that both OCT and confocal scanning laser imaging systems have particular individual advantages.
On one hand, OCT provides a high axial imaging resolution of the order of about 10 microns which is determined by the coherence length of the light source used. This technology is particularly useful for diagnostics that requires high depth resolution tomographic imaging [Fujimoto, J. G. et al. (2000) “Optical Coherence Tomography: An Emerging Technology for Biomedical Imaging and Optical Biopsy” Neoplasia, 2, 9-25; Rollins A. M. et al. (2002) “Emerging Clinical Applications of Optical Coherence Tomography” Optics and Photonics News, 13(4): 36-41; Fujimoto, J. G. (2003) “Optical coherence tomography for ultrahigh resolution in vivo imaging.” Nat Biotechnol 21(11): 1361-1367]. Meanwhile, attempts have also been made to produce en-face OCT images that look like the retinal images from an ophthalmoscope for anatomic mapping of a biological sample [Podoleanu, A. G., G. M. Dobre, et al. (1997). “Simultaneous en-face imaging of two layers in the human retina by low-coherence reflectometry.” Optics Letters 22(13): 1039-1041; Podoleanu, A. G., G. M. Dobre, et al. (1998). “En-face coherence imaging using galvanometer scanner modulation.” Optics Letters 23(3): 147-149]. However, one disadvantage associated with an OCT image is that the image is very fragmented and is sometimes difficult to interpret, leading to difficulty in terms of identifying anatomic structures.
On the other hand, confocal scanning laser imaging has been successfully applied to retinal imaging and is now well accepted by ophthalmologists in imaging the anatomic structures of the retina [see for example, Sharp, P. F. et al (2004) “The scanning laser ophthalmoscope—a review of its role in bioscience and medicine” Physics in Medicine and Biology 49: 1085-1096]. As the depth resolution of a CSLO is determined by the depth of focus of the confocal optics, a CSLO has a typical axial resolution of about 300 microns.
It was realized some years ago that a simultaneous generation of both an OCT image and a CSLO image having a pixel-to-pixel registration correspondence would not only offer the advantages of both imaging techniques but also solve the two problems of registering a three dimensional (3D) OCT image to en-face images of the same tissue, and of correcting for OCT image distortion caused by the movement of the sample such as an eye. This is because in order to generate a 3D OCT data set of a sample, it is necessary to properly register each slice of many transverse scans (B-scans) or en-face scans (C-scans) which may be misaligned due to the sample movement in between each scans and then stack them accordingly. Therefore, a simultaneous generation of both an OCT image and a CSLO image with pixel-to-pixel registration correspondence is especially useful.
One of the major benefits of combining OCT and CSLO is that they have different depth ranges. In principle OCT can be used to measure optical reflectivity at a dense set of points covering a volume of interest, and then the OCT data can be reduced to simulate the en-face image that would be seen by a CSLO or other ophthalmoscope. However OCT collection optics generally collect less sample-returned light than do CSLO collection optics. As is well known in the art, OCT is an interference-based technique so only light that is spatially coherent contributes to the signal. Often the sample-returned light is collected for OCT in a single-mode optical fiber. Reflected light which does not couple into that single mode, either by falling outside the fiber core or by entering at too steep an angle, is rejected.
Often the greater part by far of the light reflected from the sample is rejected in this way.
Nevertheless, attempts have been made to directly use the OCT configuration to generate both an OCT image and a CSLO image. In a first approach, the reference light of an OCT interferometer was alternately temporarily blocked to generate a CSLO signal, and restored to generate an OCT signal. However, this approach results in sequential, rather than simultaneous, acquisition of the OCT and CSLO images. Attempts were also made to directly use the OCT signal without blocking the OCT reference arm to simultaneously create, in addition to an OCT image, an anatomic structure image with an appearance similar to that of a CSLO image. In this respect, one approach involves the integration, or superposition on top of one another, of a multiple number of the standard OCT signals along the depth dimension. This integration is used to obtain an averaged overall depth reflectivity for each transverse pixel to generate an en-face image [Hitzenberger, C. K. et al. (2003). “Three-dimensional imaging of the human retina by high-speed optical coherence tomography.” Optics Express 11(21): 2753-2761]. Another approach uses multiple light sources of different coherence lengths to simultaneously generate multiple OCT images of different depth resolutions. Still another approach uses low pass electronic filtering of the OCT signal to extract a CSLO-like image.
All these techniques to directly use the OCT configuration to generate both an OCT image and a CSLO image collect light through a small pin-hole defined by the core size of a single mode fiber (of the order of 10 micron with a small numerical aperture (NA) as compared to the standard size of a CSLO pin-hole size of about 100 micron with a generally larger NA), which leads to a low signal to noise ratio for the CSLO image. Another problem associated with these approaches is that the forward propagating light can be relatively strongly reflected by the fiber end and sent to the confocal detector with a strength greater than the sample returned signal light, causing the CSLO sample signal being overwhelmed by the fiber end reflection.
A second approach that addresses the above problems is to separate the OCT and CSLO signals returned from the sample using a plate beam-splitter. Part of the returned sample light is directed to a separate pin hole for CSLO signal generation. Such a design can get rid of the problem of reflections from the fiber end, simultaneously produce the desired two images, enable the optimization of the CSLO signal to noise ratio by choice of the pin-hole size, and allow use of the same transverse scanner for both the OCT beam and the CSLO beam. Registration between the OCT and confocal images can be achieved with optical alignment of the respective detectors and the free-space beam splitter. However, due to the fact that a certain percentage of the returned sample beam is now deflected to the confocal pin-hole, there is a reduction in the OCT signal strength. Meanwhile, a significant amount of the returned sample beam is lost in the cladding of the OCT single mode fiber, which light could have been used for CSLO imaging.
It is desirable to have a solution that both overcomes the above-mentioned limitations and also reduces the cost of the system. It is clear from the-above analysis that the key issue is to optimize the optical power efficiency for the two images so that the signal to noise ratio for both the OCT and the CSLO images can approach the maximum achievable values as offered by each stand-alone system.
In this invention, a novel dual-waveguiding module is disclosed for both highly efficient collection as well as highly efficient separation of the OCT and CSLO signals. As a result of the present invention, highly efficient optical power usage and hence high signal to noise ratio are achieved together with inherent pixel-to-pixel registration of the OCT and CSLO images and a cost reduction of an OCT/CSLO combo system. In a preferred embodiment of the invention, a concentric single-mode/multi-mode dual-waveguiding structure (e.g. a double-clad fiber) is used to simultaneously collect both the sample returned OCT and CSLO optical signals with almost the same efficiency as can be achieved by each stand-alone device. Extraction and separation of the two signals is achieved by channeling most of the multi-mode guided optical power to a CSLO detector, using single or multiple stage multi-mode coupling or other optical power extraction techniques. The non-tapped single-mode guided optical wave is further sent to a standard OCT system for OCT image generation. With this invention, the numerical aperture and the pin-hole size for the CSLO signal can be optimized for a maximum signal to noise ratio nearly as good as can be achieved in a stand-alone CSLO system, while there is no reduction to the OCT signal strength.